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Mark (Sam Neill) is a spy returning home from an espionage mission (the nature of this mission is vague, but it involves long trips abroad, cash stuffed into briefcases, and vials of secret liquids) to find that his wife, Anna (Isabelle Adjani), wants a divorce. She won't say why, but insists it's not because she's found someone else.

Though Mark would rather stay with Anna and work things out, he turns the apartment and custody of their young son, Bob, over to her. Living alone, he begins to obsess over her, making dozens of calls, and seemingly going mad. He pays a visit to their flat only to find Bob alone, unkempt, and neglected. When Anna returns, he refuses to leave her alone with the child but attempts to make amends. He stays at the apartment to care for Bob but Anna leaves in the middle of the night.

Mark receives a phone call from Anna’s lover, Heinrich (Heinz Bennent), telling him that Anna is with him. He then gets Heinrich’s phone number from Anna’s friend, Margie. The next day, Mark meets Bob’s teacher, Helen, also played by Ms. Adjani. She looks exactly like Anna but with brilliant green eyes and is calm and kind where Anna is hysterical.

Mark pays a visit to Heinrich who swears he didn’t call telling Mark that Anna needed space; he has not seen her, having been away on a business trip himself. Mark attacks Heinrich but is beaten bloody by Heinrich.

Mark returns home to find Anna who is vague on her whereabouts when confronted. He beats her and she storms out but he follows, apologizing, attempting for reconciliation. She leaves him alone on the street. On his way back to the flat, he encounters Margie, whose left leg is in a cast, and he tells her, “I loathe you” when she offers to look after Bob. Mark has a meeting with a private investigator, then returns to the flat where he and Margie embrace in the bedroom.

The next day, Mark and Anna have another extreme argument during which she cuts her own neck with an electric knife. Mark tends the wound and then sits, forlornly in the kitchen, cutting his own arm with the knife. She leaves again – going off to her mysterious place, her neck bandaged.

Following Anna around the city, the private investigator soon discovers Anna's other apartment. The investigator informs Mark of his discovery, then enters the apartment, posing as a building manager. He is astonished to find a bizarre creature in the bathroom. Anna kills the investigator with a broken bottle.

Meanwhile, Mark begins a relationship with Helen. When she stays the night, Bob is awakened by nightmares, crying out for his mother. Helen apologizes and leaves saying she should not have attempted to replace Anna.

Zimmerman, the lover of the missing private detective, approaches Mark to inquire about his whereabouts. Mark gives him the address of Anna’s mysterious apartment. When Zimmerman goes to Anna’s apartment, he discovers the freakish creature as well as his dead lover’s body. Anna proclaims that the creature, “Is very tired. He made love to me all night,” and “He’s still unfinished, you know.” And then violently beats Zimmerman when he attempts to shoot her.

Anna, returning to the flat she shares with Mark, continues her erratic behavior, putting clothes in the refrigerator and food in the bedroom. She then tells Mark about her miscarriage, which she credits for causing her nervous breakdown. In a flashback, Anna, on her way home from market, has what appears to be a seizure of epic violence as she walks through the subway, which ends with her on the floor of the passageway, oozing blood and fluids from every orifice. She tells Mark, “What I miscarried there was sister faith and what was left was sister chance.”

She leaves him again and Mark calls Heinrich, giving him Anna’s address. He attempts to make love to her but finds the creature, now more developed but still monstrous, in her bedroom. Anna then reveals the grim fruits of her endeavors: a collection of body parts in her refrigerator, presumably those of the dead detective and Zimmerman. She attacks Heinrich with a knife and he flees, bleeding, to a pay phone to call Mark. Anna, meanwhile, prepares to make love to the creature.

Heinrich tells Mark what he has seen and begs to be picked up from the closest bar. Mark goes to Anna's apartment first and discovers the remains in the refrigerator, but it appears as if the creature is gone. He then crosses to the bar where he murders Heinrich in the bathroom, making it look as if he drowned in his own vomit. He then returns to Anna's apartment and destroys it by igniting the gas stove and blowing the place up. He escapes on Heinrich's abandoned motorcycle.

Upon returning to his flat, Mark finds Margie outside with her throat cut, possibly at Anna’s hand. He brings the body back into the flat where Anna waits. She greets him tenderly, cleans him up and makes love to him in the kitchen. He lays out a plan for them to cover up the problem and, as Bob awakens to find them together, she flees. Mark tells her to hide at Margie's place while he disposes of Margie's body.

Heinrich’s mother phones Mark looking for her son. She tells Mark that Heinrich’s body was discovered but that she did not identify it because it was only his body, “his soul was not there.”

Mark, who has continued to cover for Anna, finds her at Margie's apartment where the creature, considerably more evolved, copulates with her on the bed. As the creature penetrates her she repeats over and over, “Almost.”

Mark meets Heinrich’s mother in person and she claims that she “must be with him.” She then seemingly poisons herself and dies.

The next day, as Mark wanders the street, he meets up with his former business associates. They insist that he do business with them again. Mark appears to refuse and flees on Heinrich's motorcycle.

He returns to Margie's apartment to find it surrounded by both police and his former employers. He stages a distraction, allowing someone, possibly Anna, to sneak away in Mark's car, but Mark is wounded in the ensuing shootout.

Once again fleeing, he has a horrific accident and races into a building where he is pursued by Anna, the police and his business associates. Anna tells him, “I wanted to find you. It is finished now,” and reveals the creature, now fully formed as Mark’s doppelganger. Mark raises his gun to shoot it but he and Anna are gunned down by a hail of bullets from below as the doppelganger remains impervious. Bloodied and dying, Anna lies atop Mark and uses his gun to shoot herself in the back. She dies in his arms and he jumps to his death through the stairwell. The doppelganger flees through the roof.

Later, Helen is at the flat with Bob when the doorbell rings. Bob repeats over and over, “Don’t open,” but Helen ignores his plea. She goes to the door as the sounds of sirens, planes and explosions fill the air. Bob races through the flat, ending in the bathroom where he jumps face down into a bathtub full of water and floats as if dead. Meanwhile, Helen, listening to the sirens and planes as if in fear, seems unaware of the doppelganger which can be seen through the glass door. Her expression changes to something indeterminate as light from the explosions illuminate her brilliant, green eyes.

The film was also very controversial when first released, and heavily edited for distribution in the United States. After an initial limited theatre release in the United Kingdom, Possession was banned as one of the notorious Video Nasties, although it was later released uncut on VHS in 1999. It gradually developed a minor cult following among arthouse aficionados.

Vincent Canby of The New York Times wrote, "Possession is a veritable carnival of nose bleeds. Because the three leading characters – Anna, her husband, Marc (Sam Neill), and her lover, Heinrich (Heinz Bennent) – all knock each other violently around, they play most of their scenes in one state of bloodiness or another. At times, the living-color Possession recalls Roman Polanski's black-and-white Repulsion, though only because Miss Adjani is required to slice up as many male victims as Catherine Deneuve did in the earlier, far better film."[6]

Michael Brooke of Sight & Sound commented, "Although it’s easy to see why it was pigeonholed as a horror film, its first half presents what is still one of the most viscerally vivid portraits of a disintegrating relationship yet committed to film, comfortably rivalling Lars von Trier’sAntichrist, David Cronenberg’sThe Brood and Ingmar Bergman’sScenes from a Marriage."[7] Reviewing the Blu-ray release of the movie in 2013 Michael Dodd of Bring The Noise UK was similarly impressed with what he called "an intense exploration of marital breakdown". He argued that this made Possession "one of the few horror films that successfully builds a back story for its main characters".[8]

Variety said, "Possession starts on a hysterical note, stays there and surpasses it as the film progresses. There are excesses on all fronts: in supposedly ordinary married life and then occult happenings, intricate political skulduggery with the infamous Berlin Wall as background – they all abound in this horror-cum-political-cum – psychological tale."[9]